Human
prion diseases like
Creutzfeldt-Jakob disease are infectious, inherited, or sporadic
neurodegenerative disorders, characterized by the accumulation of an abnormal
isoform of the host-encoded
prion protein. This affects nervous tissue in
sporadic Creutzfeldt-Jakob disease and, additionally, in lymphoid tissue in
bovine spongiform encephalopathy-linked
variant Creutzfeldt-Jakob disease. Experimental studies have established the involvement of cells of the lymphoid and peripheral nervous system in the transport of
prions to their target central nervous system tissue. To evaluate the role of vessel wall-associated mobile cells, we obtained
formalin-fixed tissue blocks from various brain regions and/or basal arteries from sporadic, variant and iatrogenic
Creutzfeldt-Jakob disease, and unselected control cases. We demonstrate disease-associated
prion protein deposits in intracranial vessel walls, in sporadic and
variant Creutzfeldt-Jakob disease by performing immunohistochemical staining and
paraffin-embedded tissue blotting. Using double immunofluorescence, these deposits co-localize with
HLA-DR and S-100 immunoreactive cells in the intima, which are components of the vascular-associated dendritic cell network, as well as with
HLA-DR and CD-68 immunopositive macrophages of the intima and media. We conclude that mobile cells in vessel walls like dendritic and monocyte/macrophage lineage cells may be involved in spread of disease-associated
prion protein and possibly also of infectivity.